This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Angelman syndrom (AS) is a nuerological disorder that causes global developmental delay, minimal or absent speech, seizures, uncoordinated gait (ataxia), sleep disturbances, and other medical and behavioral difficulties. AS is caused by deficiency of the maternally-transmitted gene that encodes E6-AP ubiquitin-protein ligase (gene symbol UBE3A) mapping to chromosome 15q11-q13. Although some aspects of AS are well known to the medical community, the natural history of AS has not been systematically described. Since AS is a rare disorder, few physicians follow more than a handful of patients at any given Center. A collaborative effort is needed to better understand the natural history of this rare condition. It is only with this knowledge that we will be able to formulate treatment interventions, devise therapies and propose future clinical trials. This study is part of an initiative under the auspices of the Rare Disease Clinical Research Netrowk and the NIH. This study is designed to conduct longitudinal multidisciplinary investigations on the natural history, morbidity and mortality of Angelman Syndrome (AS). We will collect detailed longitudinal data on a cohort of AS individuals to gain a better understanding of the disease progression, and follow the natural history of the clinical features of this patient cohort including assessment of quality of life and longevity.